Aug 5, 2016

DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy

Nature Communications
Carolina GrecoGianluigi Condorelli

Abstract

Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC)-5-mC's oxidation product-in cardiac biology and disease is unknown. Here we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks the body of highly expressed genes as well as distal regulatory regions with enhanced activity. Moreover, pathological hypertrophy is characterized by a shift towards a neonatal 5-hmC distribution pattern. We also show that the ten-eleven translocation 2 (TET2) enzyme regulates the expression of key cardiac genes, such as Myh7, through 5-hmC deposition on the gene body and at enhancers. Thus, we provide a genome-wide analysis of 5-hmC in the cardiomyocyte and suggest a role for this epigenetic modification in heart development and disease.

  • References62
  • Citations56

References

Mentioned in this Paper

Embryo
Genome-Wide Association Study
Patterns
DNA Modification Process
Gene Knockdown Techniques
Body Structure
Cardiac Hypertrophy
Protein Methylation
Genome
Genes

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